The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer’s Disease Mouse Model
Palmatine, a natural alkaloid found in various plants, has been reported to have diverse pharmacological and biological effects, including anti-inflammatory, antioxidant, and cardiovascular effects. However, the role of palmatine in mitophagy, a fundamental process crucial for maintaining mitochondr...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/22/16542 |
| _version_ | 1797458942736990208 |
|---|---|
| author | Da-Ye Lee Kang-Min Lee Jee-Hyun Um Young-Yeon Kim Dong-Hyun Kim Jeanho Yun |
| author_facet | Da-Ye Lee Kang-Min Lee Jee-Hyun Um Young-Yeon Kim Dong-Hyun Kim Jeanho Yun |
| author_sort | Da-Ye Lee |
| collection | DOAJ |
| description | Palmatine, a natural alkaloid found in various plants, has been reported to have diverse pharmacological and biological effects, including anti-inflammatory, antioxidant, and cardiovascular effects. However, the role of palmatine in mitophagy, a fundamental process crucial for maintaining mitochondrial function, remains elusive. In this study, we found that palmatine efficiently induces mitophagy in various human cell lines. Palmatine specifically induces mitophagy and subsequently stimulates mitochondrial biogenesis. Palmatine did not interfere with mitochondrial function, similar to CCCP, suggesting that palmatine is not toxic to mitochondria. Importantly, palmatine treatment alleviated mitochondrial dysfunction in PINK1-knockout MEFs. Moreover, the administration of palmatine resulted in significant improvements in cognitive function and restored mitochondrial function in an Alzheimer’s disease mouse model. This study identifies palmatine as a novel inducer of selective mitophagy. Our results suggest that palmatine-mediated mitophagy induction could be a potential strategy for Alzheimer’s disease treatment and that natural alkaloids are potential sources of mitophagy inducers. |
| first_indexed | 2024-03-09T16:45:23Z |
| format | Article |
| id | doaj.art-cfc769fa814544d7b826dc59814560b8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:45:23Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cfc769fa814544d7b826dc59814560b82023-11-24T14:48:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221654210.3390/ijms242216542The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer’s Disease Mouse ModelDa-Ye Lee0Kang-Min Lee1Jee-Hyun Um2Young-Yeon Kim3Dong-Hyun Kim4Jeanho Yun5Department of Biochemistry, College of Medicine, Dong-A University, Busan 49201, Republic of KoreaDepartment of Biochemistry, College of Medicine, Dong-A University, Busan 49201, Republic of KoreaDepartment of Biochemistry, College of Medicine, Dong-A University, Busan 49201, Republic of KoreaDepartment of Biochemistry, College of Medicine, Dong-A University, Busan 49201, Republic of KoreaDepartment of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University, Seoul 05029, Republic of KoreaDepartment of Biochemistry, College of Medicine, Dong-A University, Busan 49201, Republic of KoreaPalmatine, a natural alkaloid found in various plants, has been reported to have diverse pharmacological and biological effects, including anti-inflammatory, antioxidant, and cardiovascular effects. However, the role of palmatine in mitophagy, a fundamental process crucial for maintaining mitochondrial function, remains elusive. In this study, we found that palmatine efficiently induces mitophagy in various human cell lines. Palmatine specifically induces mitophagy and subsequently stimulates mitochondrial biogenesis. Palmatine did not interfere with mitochondrial function, similar to CCCP, suggesting that palmatine is not toxic to mitochondria. Importantly, palmatine treatment alleviated mitochondrial dysfunction in PINK1-knockout MEFs. Moreover, the administration of palmatine resulted in significant improvements in cognitive function and restored mitochondrial function in an Alzheimer’s disease mouse model. This study identifies palmatine as a novel inducer of selective mitophagy. Our results suggest that palmatine-mediated mitophagy induction could be a potential strategy for Alzheimer’s disease treatment and that natural alkaloids are potential sources of mitophagy inducers.https://www.mdpi.com/1422-0067/24/22/16542palmatinemitophagymitochondrial dysfunctionAlzheimer’s disease |
| spellingShingle | Da-Ye Lee Kang-Min Lee Jee-Hyun Um Young-Yeon Kim Dong-Hyun Kim Jeanho Yun The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer’s Disease Mouse Model International Journal of Molecular Sciences palmatine mitophagy mitochondrial dysfunction Alzheimer’s disease |
| title | The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer’s Disease Mouse Model |
| title_full | The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer’s Disease Mouse Model |
| title_fullStr | The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer’s Disease Mouse Model |
| title_full_unstemmed | The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer’s Disease Mouse Model |
| title_short | The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer’s Disease Mouse Model |
| title_sort | natural alkaloid palmatine selectively induces mitophagy and restores mitochondrial function in an alzheimer s disease mouse model |
| topic | palmatine mitophagy mitochondrial dysfunction Alzheimer’s disease |
| url | https://www.mdpi.com/1422-0067/24/22/16542 |
| work_keys_str_mv | AT dayelee thenaturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT kangminlee thenaturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT jeehyunum thenaturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT youngyeonkim thenaturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT donghyunkim thenaturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT jeanhoyun thenaturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT dayelee naturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT kangminlee naturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT jeehyunum naturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT youngyeonkim naturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT donghyunkim naturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel AT jeanhoyun naturalalkaloidpalmatineselectivelyinducesmitophagyandrestoresmitochondrialfunctioninanalzheimersdiseasemousemodel |